María Isabel Hodgson

Gestational diabetes and pre‐pregnancy overweight: Possible factors involved in newborn macrosomia

Aim:  Good glycemic control in gestational diabetes mellitus (GDM) seems not to be enough to prevent macrosomia (large‐for‐gestational‐age newborns). In GDM pregnancies we studied the effects of glycemic control (as glycosylated hemoglobin [HbA1c]), pre‐pregnancy body mass index (PP‐BMI) and gestational weight gain per week (GWG‐W) on the frequency of macrosomia.

Melanocortin-4 Receptor Gene Variation Is Associated with Eating Behavior in Chilean Adults

Background/Aims: To evaluate the association between allelic variants of melanocortin receptors -3 and -4 (MC3R and MC4R, respectively) and leptin receptor (LEPR) genes with body mass index (BMI) and eating behavior. Methods: We selected 344 Chilean adults (57.8% women; age 39.1 ± 6.6 years) with a wide variation in BMI (30.3 ± 6.3 kg/m2). The Three-Factor Eating Questionnaire-R18 that measures uncontrolled eating (UE), emotional eating (EE) and cognitive restraint scores was adapted, validated and assessed for association with BMI. Genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism techniques and Taqman assays. Results: Higher EE scores were found in obese vs. non-obese in both men (p = 0.01) and women (p < 0.001). UE scores were significantly associated with BMI only in women (p = 0.002). No significant differences in eating behavior scores or BMI were found by LEPR (rs1137101, rs8179183 and rs1137100 polymorphisms) or MC3R (rs3746619 and rs3827103). Carriers of the C allele for MC4R rs17782313 showed significantly higher scores of UE compared to non-carriers (2.3 ± 0.8 vs. 2.0 ± 0.7; p = 0.02). Additionally, we also report a monogenic case of obesity carrying the pathogenic mutation 449C>T (Thr150Ile) in MC4R gene with no apparent alterations in eating behavior scores. Conclusions: UE scores were higher in C-allele carriers of MC4R-rs17782313 compared to non-carriers.

Prevalence of metabolic syndrome in obese Chilean children and association with gene variants of the leptin-melanocortin system.

Abstract Metabolic syndrome (MS) related to adult type 2 diabetes mellitus and cardiovascular disease is prevalent among obese children/adolescents. Genetic variants of the leptin-melanocortin system have been associated with components of MS. The aim of our study is to estimate the prevalence of MS (according to Cook’s criteria) in a Chilean cross-sectional sample of 259 obese children (47.1% girls, aged 6–12 years), and to assess the association between common genetic variants of leptin-melanocortin pathway genes (LEP, LEPR, POMC, MC3R and MC4R) with components of the MS using logistic regression. We observed an overall MS prevalence of 26.3% (32.2% in girls and 21.1% in boys) in obese Chilean children. No associations were detected between genetic variants of leptin-melanocortin genes and MS components. MS prevalence among our obese children sample is similar to those previously described in Chile, demonstrating the increased risk of diseases in adulthood that obese children carry.

Divergent metabolic phenotype between two sisters with congenital generalized lipodystrophy due to double AGPAT2 homozygous mutations. a clinical, genetic and in silico study.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by extreme reduction of white adipose tissue (WAT) mass. CGL type 1 is the most frequent form and is caused by mutations in AGPAT2. Genetic and clinical studies were performed in two affected sisters of a Chilean family. These patients have notoriously dissimilar metabolic abnormalities that correlate with differential levels of circulating leptin and soluble leptin receptor fraction. Sequencing of AGPAT2 exons and exon-intron boundaries revealed two homozygous mutations in both sisters. Missense mutation c.299G>A changes a conserved serine in the acyltransferase NHX4D motif of AGPAT2 (p.Ser100Asn). Intronic c.493-1G>C mutation destroy a conserved splicing site that likely leads to exon 4 skipping and deletion of whole AGPAT2 substrate binding domain. In silico protein modeling provided insights of the mechanisms of lack of catalytic activity owing to both mutations.

Bone mineral density in young Chilean patients with type 1 diabetes mellitus

Abstract Background: In this study, our aim was to analyze bone mineral density (BMD) in patients with type 1 diabetes mellitus (T1DM) and compare them with a healthy reference population; in addition, we aimed to observe the association between BMD and the following variables: age at onset, disease duration, metabolic control, pubertal stage, level of physical activity, clinical parameters and nutrient intake. Methods: A total of 30 patients with T1DM were included in the study. BMD was determined using dual-energy X-ray densitometry (DXA). Participants with a z-score of values ≥–1 were accepted as normal; BMDs between –2 and –1 were defined as being in the low range of normality; ≤–2 were defined as having low BMD. The 25-hydroxy vitamin D level was classified as sufficient (30–100 ng/mL), insufficient (20–30 ng/mL), and deficient (<20 ng/mL). Results: The percentages of patients with deficient and insufficient 25(OH) vitamin D levels were 50% and 45.8%, respectively. Lumbar spine (LS2–LS4) BMD, total body (TB) BMD and femoral neck (FN) BMD were found in the normal range for more than 80% of the subjects, with no significant differences due to gender. No strong correlations between clinical variables, biochemical parameters and nutrient intake were observed; however, a moderate positive correlation was found between serum calcium and LS2–LS4 BMD (p<0.05). Regression analysis showed that serum calcium, duration of diabetes and intake of sodium and protein are significant factors in determining LS2–LS4 BMD and TB BMD. Conclusions: Patients with T1DM had a normal mean BMD at all sites evaluated, except for two patients who had low BMD at the lumbar spine. More than 95% of patients had insufficient or deficient vitamin D levels. With respect to all the variables studied, serum calcium presented the highest significant correlation with LS2–LS4 BMD.

Nuevas proyecciones fisiológicas, patológicas y terapéuticas de la leptina

The adipose tissue is an endocrine organ that produces a variety of protein hormones. One of them is leptin, which regulates several critical functions at the central nervous system such as caloric intake, basal energy expenditure, reproduction, glucose and lipid metabolism and osteogenesis. Acting at a local level, leptin modulates the immune system and promotes liver fibrogenesis. The most promising therapeutic implications of leptin will possibly be in type 1 diabetes mellitus (DM1). Its supplementation in animal models of DM1 prevents hyperglycemia and ketoacidosis. These actions depend on the activation of leptin receptors in the central nervous system and the suppression of glucagon signaling in the liver.The adipose tissue is an endocrine organ that produces a variety of protein hormones. One of them is leptin, which regulates several critical functions at the central nervous system such as caloric intake, basal energy expenditure, reproduction, glucose and lipid metabolism and osteogenesis. Acting at a local level, leptin modulates the immune system and promotes liver fibrogenesis. The most promising therapeutic implications of leptin will possibly be in type 1 diabetes mellitus (DM1). Its supplementation in animal models of DM1 prevents hyperglycemia and ketoacidosis. These actions depend on the activation of leptin receptors in the central nervous system and the suppression of glucagon signaling in the liver.

Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus

Abstract Objective: The aim of this study was to assess dietary intake, nutritional status, body composition, and physical activity level in a group of Chilean children and adolescents with Type 1 diabetes mellitus (T1DM), compare these parameters with the recommendations of the International Society for Pediatric and Adolescent Diabetes (ISPAD), and determine the relationships between dietary intake, body composition, and diabetes control. Methods: A total of 30 patients with T1DM (aged 15.2±4.0 years) were included. Dietary intake was assessed using a 92-item quantitative food frequency questionnaire. Body composition was determined using dual-energy X-ray densitometry. Physical activity was assessed by means of a survey. Results: The energy intake of these patients was derived from 21.4% protein, 48% carbohydrates, and 31.2% fat. The glycosylated hemoglobin (HbA1c) was significantly correlated with fat as grams per day (r: 0.363, p<0.05) and calories per day (r: 0.364, p<0.05). The mean body fat percentage in females was 31.2% and 20.2% in males (p < 0.01) and the mean amount of physical activity was 4.5±2.7 h per week. Conclusions: The study patients had a higher protein intake than recommended by ISPAD. Dietary carbohydrate intake was rather low, and dietary fat intake was the same as the limits recommended by ISPAD. Diabetic control was significantly correlated with protein, carbohydrates, fat, and sodium intake. The girls in the study had a higher percentage of body fat than the standard recommendations for their age. The level of physical activity was adequate.

Evaluación nutricional en niños hospitalizados en un Servicio de Pediatría

INTRODUCTION Malnutrition in hospitalized children is associated with increased morbidity and mortality. OBJECTIVE To determine the nutritional status in children admitted to the Hospital Clínico de la Universidad Católica de Chile. PATIENTS AND METHOD A retrospective, cross-sectional study was conducted on hospital patients less than 17 years old within the period from November 2010 to April 2011. A record was made of the demographic data, admission diagnosis, biochemistry results (albumin, haemoglobin, haematocrit), hospital stay, and anthropometry data. Nutritional diagnosis was expressed as standard deviation (SD) for weight-for-height (WFH) by WHO in children younger than 5 y, and body mass index (BMI) by CDC-NCHS in older children. Height-for-age (HFA) ≤-2SD indicated stunted growth. RESULTS A total of 365 children, including 201 boys (55.1%), were evaluated. The median age was 3.35 years (IQR: 1.2-8.2). The most frequent reason for admission was heart disease (30.4%). The median hospital stay was 2 days (IQR: 2.0-4.0). Undernutrition was observed in 3.3% of the children, 8% were nutritionally at risk, 15% were overweight, and 10.9% were obese. As regards HFA, short stature was reported in 12.9%. There was a significant relationship between lower age and heart disease, and higher age with gastrointestinal and neurological diseases. By ordinal logistic regression for each year of age, the weight/height ratio (ZP/T) increases by 6.9% (OR=1.07). The biochemistry results (albumin, haemoglobin and haematocrit levels) were not associated with nutritional status. CONCLUSIONS A high percentage of children at risk of undernutrition was found. The percentage overweight was similar to the general Chilean paediatric population. Early detection will allow an opportune intervention, and nutritional monitoring at discharge.

A126: Clusters of Autoimmune Diseases in Children and the Role of PTPN22 C1858T Gene Polymorphism in Pediatric Polyautoimmunity

Autoimmune diseases (AIDs) have familial aggregation and frequently share a common genetic background, but few studies have evaluated autoimmune clusters in children with AIDs and their families. Children with more than one AID (pediatric polyautoimmunity) may have a stronger genetic component than children with a single AID. The objectives of this study were to identify clusters of AIDs in children and their first‐degree relatives and to evaluate the association of PTPN22 C1858T gene polymorphism with pediatric polyautoimmunity.